1. Technical Field
The present invention relates to a method for the production of solidified particles from a liquid raw material, wherein individual liquid volumes are separated from the liquid raw material on a portion-by-portion basis and these portioned liquid volumes are introduced into an environment which is effective to solidify the individual particles, and it also relates to devices used for this purpose.
2. Related Art
Solid particles or micro-particles produced from liquid media can be used in the fields of medicine, pharmaceuticals, biotechnology, agro-chemistry, as well as in the food and chemical industries. Thus, for this purpose, selected active substances can be introduced into a carrier medium which, initially, is in the liquid state. In a subsequent processing step, the carrier medium together with the active substance is portioned in the form of liquid precursor droplets and fed into an environment which is effective to solidify the liquid precursor droplets. The active substances, which are now present in the form of solidified and structurally hardened particles, exhibit advantageous chemical, biological and/or physical properties in dependence on the type of active substance as well as on the shape, size and distribution of the micro-particles.
Carrier media for the production of solid particles by means of a process involving the solidification of liquid precursor droplets are known. Hereby, these may, for example, be monomer and polymer liquids, ionic cross-linked gels (sodium alginate for example), thermally cross-linked gels (agar agar for example), gelatine, metallic oxides, hydroxyl cellulose, polyvinyl alcohol, waxes, resins, melts, etc.
Media for the solidification of such carrier media are likewise generally known. Thus, the solidification or gelling of sodium alginate can take place in the presence of potassium or calcium ions which are present in a so-called cross-linking solution in a catching bath.
Devices are also known wherein the liquid used for the production of the solid particles is fed-in in the form of a jet through appropriately designed nozzles and the fluid jet is divided up or atomised into individual separate drops immediately after flowing through the nozzle body.
A device, in which the dividing process takes place by means of a vibratory action, is known from DE 2 221 310 C2. The division into drops is effected by means of a nozzle arrangement connected to a vibratory drive. The drops are collected and solidified in a downstream reaction vessel.
A device for the production of spherical granulates by vibratory or oscillatory stimulation is described in DE 196 17 924 A1. The formation of the individual drops is obtained by directly stimulating the liquid that is to be turned into drops by means of an oscillatory process. Here, the transmission of the oscillation to the liquid is effected by means of a resilient body which has been caused to oscillate or by the introduction of a piezo-electric crystal or an ultrasonic probe.
In DE 34 17 899 C1 for example, it is described how liquids can be atomised with the aid of a rotating cylinder having openings formed in the cylinder wall. Drops are hurled into an cross-linking solution through the appropriate openings. The cross-linking solution is located in a container that is likewise mounted in rotary manner around the cylinder and, due to the rotation, forms a parabolic fluid mirror via which the droplets being spun out from the cylinder wall enter the cross-linking solution for the hardening process.
A device is known from DE 44 24 998 C2, wherein a full jet of fluid initially emerges under pressure from a nozzle and is divided up into individual sections in a subsequent step by means of a divider device. The formation of the liquid sections is effected in that liquid portions are periodically expelled from the fluid jet by means of the divider device thereby forming drop-shaped elements. Only that part which remains in the jet reaches the solidification process, the expelled portion representing a cutting or spraying loss.
Other devices for the production and portioned discharge of small drops are known from ink jet printer technology. Here, the discharge of the ink droplets is caused by inducing a displacement of the liquid. This displacement may be effected piezo-electrically by the deformation of a body, thermoelectrically by the production of a vapour bubble (WO 96/32242 for example), by the production of an acoustic pressure wave or electro-dynamically by the rotary movement of a paddle in a magnetic field (U.S. Pat. No. 4,150,201 for example).
In the conventional processes, the viscosity of the starting liquids represents a limiting factor for each of these methods, so that either only low viscosity liquids or only high viscosity liquids can be processed. Furthermore, the production of droplets having a mono-dispersed size distribution is a problem due to the unpredictable variation in the way the individual droplets coalesce into a larger droplet. In addition, the production of droplets having a centred core and a cladding liquid is only possible to a limited extent, or is not possible at all. Moreover, it is desirable to increase the scale of production such as the throughput quantities as well as to prevent losses of the starting medium caused by the techniques being used.